The present invention relates to a matrix suitable for transdermal administering of rotigotine [(−)-5,6,7,8-tetrahydro-6-[propyl[2-(2-thienyl)ethyl]amino]-1-naphtol] that is free of solubilizers and dispersants and that comprises at least one matrix polymer and rotigotine base in a concentration above the solubility limit of the matrix polymer for rotigotine, wherein the portion of the rotigotine not dissolved in the matrix polymer is dispersed in the matrix polymer as amorphous particles with a maximum mean diameter of 30 μm.
Furthermore, the invention relates to a planiform system for transdermal administering of rotigotine, that contains the above-described preferably silicon-based matrix supersaturated with rotigotine and a backing impermeable for the active substance.
Various silicon-based transdermal systems for administering rotigotine are known from the state of the art.
WO 94-07468 discloses a transdermal system that contains an active substance salt in a two-phase matrix. The two-phase matrix consists of a hydrophobic matrix polymer with a silicate dispersed therein to absorb the hydrophilic pharmaceutical substance salt, wherein hydrophobic solvents are additionally used. The matrix is produced by drying the dispersion at 70° C. The rotigotine content in the matrix is 2-5 weight percent.
This system has several disadvantages, however:                The production is in several stages and expensive. The active substance must be dissolved, then mixed with the silicate, then mixed with an emulsifier, in order to finally emulsify e.g. in a silicon contact adhesive, the solution with the matrix polymer dissolved in an organic solvent—typically heptane, ethyl acetate or toluol.        The resulting emulsion is difficult to handle.        The active substance charge is limited by the solubility of the rotigotine in the respective solvent system. In addition, when removing the solvent during production a concentration takes place, during which an undesirable crystal formation may occur. The maximum quantity of active substance that can be worked into the matrix is limited by this as well. On the other hand, a low active substance charge limits the release capacity of the matrix per unit of time and/or its useful life.        The silicate or silicon dioxide remaining in the plaster represents a diffusion barrier for the active substance, which can negatively affect the release of the active substance.        The anorganic silicate influences the water absorption of the plaster. Pore formation by the dissolving away of water soluble matrix components at the boundary surface adjacent to the skin can lead to a poorly controllable release of the active substance.        
WO 99/49852 describes a Transdermal Therapeutic System (TTS) containing a contact adhesive system based on acrylate or silicon, in which rotigotine is present in free-base form. The disclosed TTS allows therapeutically relevant flow rates of rotigotine through human skin.
Rotigotine is only feebly soluble in hydrophobic polymers such as silicon, for example. For these reasons, in WO 99/49852 the adding of additives to improve the solution characteristics of the rotigotine is recommended. This is a matter of in particular hydrophilic polymers such as polyvinyl pyrrolidone (PVP), copolymers of vinyl pyrrolidone and vinyl acetate, polyethylene glycol polypropylene glycol, copolymers of ethylene and vinyl acetate as well as glycerin and its ester.
WO 02/089778 and WO 02/089777 also describe a solvent-based transdermal system for administering rotigotine. According to WO 02/089778 and WO 02/089777, surface-active substances or amphiphilic substances are also added as crystallization inhibitor.
It was thus the technical problem of the present invention to provide a matrix that is simply structured and contains as few accessory substances as possible, but still allows the administering of rotigotine through the skin in therapeutically relevant flow rates, is stable for storage and allows rotigotine base to be worked in a wide range of concentration levels.